(82 days)
The DiaSorin LIAISON® 1-84 PTH assay is an in vitro chemiluminescent immunoassay (CLIA) intended for the quantitative determination of parathyroid hormone (1-84) in human serum and EDTA plasma. Measurements of parathyroid hormone levels are used in the differential diagnosis of hypercalcemia resulting from disorders of calcium metabolism.
The test has to be performed on the LIAISON® Analyzer.
The DiaSorin LIAISON® 1-84 PTH Control Set is intended for in vitro diagnostic use as assayed quality control samples to monitor the accuracy and precision of the LIAISON® 1-84 PTH Assay.
The DiaSorin LIAISON® 1-84 PTH Calibration Verifiers are assayed quality control materials intended for in vitro diagnostic use in the quantitative verification of calibration and reportable range of the LIAISON® 1-84 PTH Assay.
The LIAISON® 1-84 PTH Assay is a modified two-step, two-site sandwich assay that uses two polyclonal antibodies for capture and detection of the 1-84 PTH molecule. Results are determined by a 2 point calibration conversion of the master curve to a working curve. The light signal is measured by a photomultiplier as relative light units (RLU) and is proportional to the concentration of 1-84 PTH present in the calibrators, controls or samples.
LIAISON® 1-84 PTH Control set contains;
- 2 levels controls containing human plasma spiked with 1-84 PTH, and preservatives: 4 vials each level; lyophilized
The target concentration for control level 1 is 30 pg/mL. The target concentration for control Level 2 is 260 pg/mL.
The range of concentrations of each control is reported on the certificate of analysis provided with each LIAISON® 1-84 PTH Control set.
LIAISON® 1-84 PTH Calibration Verifier set contains:
- 4 levels containing human plasma spiked with 1-84 PTH, with preservative, 1 vial each level, lyophilized.
The target concentration for cal verifier A is 10 pg/mL. The target concentration for cal verifier B is 80 pg/mL. The target concentration for cal verifier C is 400 pg/mL. The target concentration for cal verifier D is 1450 pg/mL.
The range of concentrations of each calibration verifier is reported on the certificate of analysis provided with each LIAISON® 1-84 PTH Calibration Verifier set.
This document describes the performance of the DiaSorin LIAISON® 1-84 PTH Assay, LIAISON® 1-84 PTH Control Set, and LIAISON® 1-84 PTH Calibration Verifiers, concluding they are substantially equivalent to their predicate devices.
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are not explicitly stated in the provided text as numerical targets for each performance characteristic. Instead, the study demonstrates performance by comparing the LIAISON® 1-84 PTH Assay with its predicate device and established CLSI guidelines. The performance characteristics for the LIAISON® 1-84 PTH Assay are summarized below:
| Performance Characteristic | Reported Device Performance (LIAISON® 1-84 PTH Assay) |
|---|---|
| Method Comparison | - n: 193 patient samples (comparative to Scantibodies Laboratory Inc. Whole PTH™ (1-84) Specific IRMA assay). |
- Passing & Bablok Regression (R): 0.9812 (indicates strong correlation).
- Slope: 0.9810 (95% CI: 0.9497 to 1.0204) (close to 1).
- Intercept: -2.23 pg/mL (95% CI: -5.29 to -0.61) (close to 0). |
| Sample Matrix Comparison | - n: 188 matched patient sets of EDTA plasma and serum samples. - Passing & Bablok Regression (R²): 0.9981 (between serum and EDTA plasma).
- Slope: 1.0481 (95% CI: 1.03 – 1.08).
- Intercept: 0.14 pg/mL (95% CI: -0.48 – 0.69). Comparisons indicate good agreement between sample types. |
| Reference Range | - EDTA Plasma: 5.72 - 45.4 pg/mL (Median: 25.0 pg/mL, N=125). - Serum: 5.68 - 47.8 pg/mL (Median: 25.2 pg/mL, N=124).
- Established from healthy adults (21-70 years) from mixed ethnic backgrounds in the U.S. with normal relevant health markers. |
| Precision | - Kit Control 1 (Mean 30.2 pg/mL): Total %CV 5.0% (N=160 replicates). - Kit Control 2 (Mean 305.6 pg/mL): Total %CV 4.6% (N=160 replicates).
- EDTA PTH-S1 (Mean 11.8 pg/mL): Total %CV 10.4% (N=160 replicates).
- EDTA PTH-S7 (Mean 1743.9 pg/mL): Total %CV 5.8% (N=160 replicates).
- Calibration Verifier A (Mean 13.0 pg/mL): TOTAL (Within-lot) %CV 8.2% (N=80 replicate results).
- Calibration Verifier D (Mean 1487 pg/mL): TOTAL (Within-lot) %CV 5.7% (N=80 replicate results). |
| Linearity | - Serum: Observed 1-84 PTH = 0.9992x + 0.0835; R² = 0.9976. - EDTA plasma: Observed 1-84 PTH = 0.9679x - 3.328; R² = 0.9971. (Very high R² values indicate strong linearity across the tested range). If an AI component is involved, please describe what the AI is (e.g. classification, segmentation) and what it is trying to predict |
| High Dose Hook Effect | No high dose hook effect observed for 1-84 PTH concentrations measured up to 60,000 pg/mL. |
| Recovery | Mean Recovery across various spiked EDTA plasma samples was 95%. |
| Analytical Specificity | - Very low % Cross Reactivity for all tested PTH fragments (e.g., 7-84 PTH: 0.00105%, 1-34 PTH: 0.00005%) and structurally similar proteins. |
| Interference | No significant interference (≥ ±10%) observed for a wide range of endogenous substances (e.g., Hemoglobin up to 500 mg/dL, Bilirubin up to 40 mg/dL, Triglycerides up to 3,000 mg/dL) and exogenous substances (e.g., Acetaminophen up to 20 mg/dL, Vitamin D2/D3 up to 240 ng/mL, Biotin up to 1 ug/mL) at two PTH levels (40 and 70 pg/mL). |
| Limit of Blank (LOB) | ≤ 0.5 pg/mL |
| Limit of Detection (LOD) | 1.0 pg/mL |
| Limit of Quantitation (LOQ) | 4.0 pg/mL |
| Stability | Reagent Integral: 28 days (open vial on system/at 2-8°C). Calibrators/Controls: 8 weeks (open vial reconstituted and frozen at -20°C). Calibration curve: 7 days. Calibration Verifiers: 2 weeks (open vial reconstituted and frozen at -20°C). |
| Measuring Range | 4 - 1800 pg/mL |
| Traceability | Calibrators, Controls, and Calibration Verifiers referenced to an in-house standard preparation containing synthetic human PTH (1-84). |
2. Sample Sizes Used for the Test Set and Data Provenance
- Method Comparison: 193 patient samples. The provenance is implied to be from patient samples used for laboratory testing, but specific country of origin or whether they were retrospective/prospective is not stated.
- Sample Matrix Comparison: 188 matched patient sets of EDTA plasma and serum samples. Data provenance is not explicitly stated as retrospective or prospective, nor is the country of origin.
- Reference Range: 125 EDTA plasma samples (91 females, 34 males) and 124 serum samples (90 females, 34 males) collected from "apparently healthy adults; 21 - 70 years of age, from mixed ethnic backgrounds (32.0% dark-skinned, 67.2% lightskinned and 0.8% unknown) with normal 25 OH Vitamin D, TSH, Total Calcium, Phosphorus, Magnesium, Creatinine and Alkaline Phosphatase levels from the northern and southern regions of the U.S." This indicates the data is from the United States and is prospective in nature, as samples were collected from healthy individuals to establish ranges.
- Precision:
- Coded panel (7 frozen EDTA plasma samples): 160 replicate results per sample (2 replicates per run, 2 runs per day for 20 operating days).
- Kit Controls (2 levels): 160 replicate results per control (2 replicates per run, 2 runs per day for 20 operating days).
- Calibration Verifiers (4 levels): 80 replicate results per calibration verifier (2 replicates per run, 2 runs per day for 20 operating days).
- Data provenance not specified beyond "prepared by DiaSorin Inc."
- Linearity: Not explicitly stated, but "one sample pool of each type: serum and EDTA plasma were diluted and analyzed."
- High Dose Hook Effect: Three serum and three EDTA plasma samples were used, spiked with 1-84 PTH. Measured in triplicate.
- Recovery Study: Five high concentration EDTA plasma samples and five low concentration EDTA plasma samples were analyzed.
- Analytical Specificity Cross-Reactivity Studies: Not specified, but involved spiking LIAISON® 1-84 PTH Specimen Diluent with various substances.
- Interference Studies: Not specified, but involved spiking EDTA plasma at two PTH levels (40 and 70 pg/mL) with various substances.
- Limit of Blank, Limit of Detection, Limit of Quantitation: Not specified, but determined using CLSI EP17-A2.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
For in vitro diagnostic (IVD) assays, the "ground truth" for patient samples is typically established by the reference method (either a validated predicate device or a clinical reference standard) and the inherent biological characteristics of the samples. This is not a study involving human readers or interpretation of images. Therefore:
- Number of Experts: Not applicable in the context of interpretation, as the device measures a quantitative analyte. The analytical performance is compared against a predicate device and established clinical guidelines.
- Qualifications of Experts: Not applicable in the context of interpretation. However, the studies were conducted according to CLSI guidelines, implying professionals with expertise in clinical laboratory testing and assay validation.
4. Adjudication Method for the Test Set
Not applicable. This is not a study requiring adjudication of interpretations (e.g., 2+1, 3+1). The performance is based on quantitative measurements.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
Not applicable. This document describes an in vitro diagnostic assay, not a medical imaging or AI-assisted diagnostic device that involves human readers.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
Yes, the studies presented are for the standalone performance of the LIAISON® 1-84 PTH Assay on the LIAISON® Analyzer. This is a fully automated immunoassay system; there is no "human-in-the-loop" once the samples are loaded and the assay is initiated. The reported performance characteristics (e.g., precision, linearity, accuracy against predicate) represent the algorithm's performance.
7. The Type of Ground Truth Used
The ground truth for the performance studies was established through:
- Reference Method Comparison: Comparison against the Scantibodies Laboratory, Inc. Whole PTH™ (1-84) Specific immunoradiometric (IRMA) assay (predicate device) for patient sample results.
- Spiked Samples: For linearity, high-dose hook effect, recovery, analytical specificity, and interference studies, known concentrations of PTH or interfering substances were added to samples, with the expectation that the assay would accurately measure these known concentrations.
- Healthy Donor Population: For reference range establishment, samples from apparently healthy individuals with normal levels of related biomarkers formed the basis for defined reference intervals.
- Internal Standards: The calibrators, controls, and calibration verifiers are traceable to "an in-house standard preparation containing synthetic human PTH (1-84)," serving as an internal ground truth for the assay's measurements.
8. The Sample Size for the Training Set
This document describes the validation of an IVD assay, not an AI/ML device that requires a distinct "training set" in the machine learning sense. The assay works based on established biochemical principles and does not learn from data in the same way an AI algorithm does. Therefore, a "training set" in that context is not applicable.
However, if one were to consider the data used to develop and optimize the assay parameters (prior to the validation studies reported here), that would be considered the equivalent of a "training set." The document does not specify the sample size for this developmental phase.
9. How the Ground Truth for the Training Set Was Established
As noted in point 8, the concept of a "training set" for this type of IVD, where performance is based on chemical-immunological reactions rather than machine learning, is not directly applicable. The "ground truth" during the development and optimization of such an assay would typically be established through:
- Reference materials: Highly characterized synthetic PTH or purified natural PTH standards with known concentrations.
- Validated methods: Existing, well-established reference methods for PTH measurement.
- Clinical samples: Use of patient samples with confirmed clinical states (e.g., hyperparathyroidism, hypoparathyroidism) to ensure the assay's output correlates with physiological conditions.
- Protocols following good laboratory practices and quality system regulations to ensure the accuracy and reliability of these references.
The document implicitly refers to these by stating the LIAISON® 1-84 PTH Calibrators, Controls, and Calibration Verifiers are "referenced to an in-house standard preparation containing synthetic human PTH (1-84)." This "in-house standard" would be the foundational "ground truth" for the assay's quantitative measurements.
§ 862.1545 Parathyroid hormone test system.
(a)
Identification. A parathyroid hormone test system is a device intended to measure the levels of parathyroid hormone in serum and plasma. Measurements of parathyroid hormone levels are used in the differential diagnosis of hypercalcemia (abnormally high levels of calcium in the blood) and hypocalcemia (abnormally low levels of calcium in the blood) resulting from disorders of calcium metabolism.(b)
Classification. Class II.